Through this K08 application, I request support to facilitate my transition to an independent researcher in statistical genetics as applied to nicotin dependence and comorbid psychiatric disorders. I have a foundation both in statistics and clinical psychiatry, and recent postdoctoral training in psychiatric and addiction genetics. This grant will provide me with the additional training I need in statistical genetics, data collection, grant development, and project management. Using a combination of didactic coursework and supervision with mentors in quantitative genetics (Drs. James Cheverud, and Peter Kraft), addiction genetics (Dr. Laura Bierut), molecular genetics (Dr. Alison Goate), and psychiatric genetics (Dr. Michael Owen), I will develop the expertise needed to become a successful, independent investigator. The research proposed in this application was designed to significantly contribute to the field of addiction genetics, and to complement my career development plan by leveraging the skills of my mentors to help guide me to develop an independent field of study. The three aims are (1) to calculate the proportion of phenotypic variance for nicotine dependence that is explained by the common SNPs in genome-wide association studies (GWAS) to better understand the total amount of information available in the datasets, (2) to examine homogenous subgroups of individuals and compare contrasting subgroups of individuals to find novel loci that are more strongly associated with nicotine dependence, particularly in the context of comorbid psychiatric disorders, and (3) to develop a database to maximize power for discovery of genetic variants that contribute to nicotine dependence. These studies will help me to develop a strong research program that uses my unique combination of quantitative expertise with clinical knowledge to better understand the genetics of smoking and comorbid psychiatric disorders.